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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4416-4423.
Prepublished online as a Blood First Edition Paper on February 22, 2005; DOI 10.1182/blood-2004-08-3156.
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IMMUNOBIOLOGY
A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules
Nadine C. Fernandez,
Emmanuel Treiner,
Russell E. Vance,
Amanda M. Jamieson,
Suzanne Lemieux, and
David H. Raulet
From the Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley; and the Institut National de la Recherche Scientifique–Institut Armand Frappier, Université du Québec, Laval, QC, Canada.
It is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC–specific inhibitory receptors, yet are nevertheless self-tolerant. These NK cells exhibit a normal cell surface phenotype and some functional activity. However, they respond poorly to class I–deficient normal cells, tumor cells, or cross-linking of stimulatory receptors, suggesting that self-tolerance is established by dampening stimulatory signaling. Thus, self-tolerance of NK cells in normal animals can occur independently of MHC-mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK cells, as also proposed for B and T cells.
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